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Tissue morphogenesis is driven by mechanical forces that elicit changes in cell size, shape and motion. The extent by which forces deform tissues critically depends on the rheological properties of the recipient tissue. Yet, whether and how dynamic changes in tissue rheology affect tissue morphogenesis and how they are regulated within the developing organism remain unclear. Here, we show that blastoderm spreading at the onset of zebrafish morphogenesis relies on a rapid, pronounced and spatially patterned tissue fluidization. Blastoderm fluidization is temporally controlled by mitotic cell rounding-dependent cell-cell contact disassembly during the last rounds of cell cleavages. Moreover, fluidization is spatially restricted to the central blastoderm by local activation of non-canonical Wnt signalling within the blastoderm margin, increasing cell cohesion and thereby counteracting the effect of mitotic rounding on contact disassembly. Overall, our results identify a fluidity transition mediated by loss of cell cohesion as a critical regulator of embryo morphogenesis.

The seminal observation that mechanical signals can elicit changes in biochemical signalling within cells, a process commonly termed mechanosensation and mechanotransduction, has revolutionized our understanding of the role of cell mechanics in various fundamental biological processes, such as cell motility, adhesion, proliferation and differentiation. In this Review, we will discuss how the interplay and feedback between mechanical and biochemical signals control tissue morphogenesis and cell fate specification in embryonic development.

During embryonic development, mechanical forces are essential for cellular rearrangements driving tissue morphogenesis. Here, we show that in the early zebrafish embryo, friction forces are generated at the interface between anterior axial mesoderm (prechordal plate, ppl) progenitors migrating towards the animal pole and neurectoderm progenitors moving in the opposite direction towards the vegetal pole of the embryo. These friction forces lead to global rearrangement of cells within the neurectoderm and determine the position of the neural anlage. Using a combination of experiments and simulations, we show that this process depends on hydrodynamic coupling between neurectoderm and ppl as a result of E-cadherin-mediated adhesion between those tissues. Our data thus establish the emergence of friction forces at the interface between moving tissues as a critical force-generating process shaping the embryo.

Epithelial cell layers need to be tightly regulated to maintain their integrity and correct function. Cell integration into epithelial sheets is now shown to depend on the N-WASP-regulated stabilization of cortical F-actin, which generates distinct patterns of apical-lateral contractility at E-cadherin-based cell-cell junctions.

Epithelial spreading is a common and fundamental aspect of various developmental and disease-related processes such as epithelial closure and wound healing. A key challenge for epithelial tissues undergoing spreading is to increase their surface area without disrupting epithelial integrity. Here we show that orienting cell divisions by tension constitutes an efficient mechanism by which the enveloping cell layer (EVL) releases anisotropic tension while undergoing spreading during zebrafish epiboly. The control of EVL cell-division orientation by tension involves cell elongation and requires myosin II activity to align the mitotic spindle with the main tension axis. We also found that in the absence of tension-oriented cell divisions and in the presence of increased tissue tension, EVL cells undergo ectopic fusions, suggesting that the reduction of tension anisotropy by oriented cell divisions is required to prevent EVL cells from fusing. We conclude that cell-division orientation by tension constitutes a key mechanism for limiting tension anisotropy and thus promoting tissue spreading during EVL epiboly.

Oriented mitosis is essential during tissue morphogenesis. The Wnt/planar cell polarity (Wnt/PCP) pathway orients mitosis in a number of developmental systems, including dorsal epiblast cell divisions along the animal-vegetal (A-V) axis during zebrafish gastrulation. How Wnt signalling orients the mitotic plane is, however, unknown. Here we show that, in dorsal epiblast cells, anthrax toxin receptor 2a (Antxr2a) accumulates in a polarized cortical cap, which is aligned with the embryonic A-V axis and forecasts the division plane. Filamentous actin (F-actin) also forms an A-V polarized cap, which depends on Wnt/PCP and its effectors RhoA and Rock2. Antxr2a is recruited to the cap by interacting with actin. Antxr2a also interacts with RhoA and together they activate the diaphanous-related formin zDia2. Mechanistically, Antxr2a functions as a Wnt-dependent polarized determinant, which, through the action of RhoA and zDia2, exerts torque on the spindle to align it with the A-V axis.

Cell migration is central to embryonic development, homeostasis and disease, processes in which cells move as part of a group or individually. Whereas the mechanisms controlling single-cell migration in vitro are relatively well understood, less is known about the mechanisms promoting the motility of individual cells in vivo. In particular, it is not clear how cells that form blebs in their migration use those protrusions to bring about movement in the context of the three-dimensional cellular environment. Here we show that the motility of chemokine-guided germ cells within the zebrafish embryo requires the function of the small Rho GTPases Rac1 and RhoA, as well as E-cadherin-mediated cell-cell adhesion. Using fluorescence resonance energy transfer we demonstrate that Rac1 and RhoA are activated in the cell front. At this location, Rac1 is responsible for the formation of actin-rich structures, and RhoA promotes retrograde actin flow. We propose that these actin-rich structures undergoing retrograde flow are essential for the generation of E-cadherin-mediated traction forces between the germ cells and the surrounding tissue and are therefore crucial for cell motility in vivo.

Understanding the factors that direct tissue organization during development is one of the most fundamental goals in developmental biology. Various hypotheses explain cell sorting and tissue organization on the basis of the adhesive and mechanical properties of the constituent cells. However, validating these hypotheses has been difficult due to the lack of appropriate tools to measure these parameters. Here we use atomic force microscopy (AFM) to quantify the adhesive and mechanical properties of individual ectoderm, mesoderm and endoderm progenitor cells from gastrulating zebrafish embryos. Combining these data with tissue self-assembly in vitro and the sorting behaviour of progenitors in vivo, we have shown that differential actomyosin-dependent cell-cortex tension, regulated by Nodal/TGFbeta-signalling (transforming growth factor beta), constitutes a key factor that directs progenitor-cell sorting. These results demonstrate a previously unrecognized role for Nodal-controlled cell-cortex tension in germ-layer organization during gastrulation.